1.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
2.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
3.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
4.Correlation of life events with depression, anxiety and somatic symptoms in graduate students: a study based on network analysis
Weili DENG ; Jia CAI ; Qiuyue LYV ; Qianshu MA ; Yupeng LUO ; Min XIE ; Qiang WANG
Sichuan Mental Health 2025;38(4):364-373
BackgroundGraduate students frequently face life events, many of which may adversely affect their mental well-being. However, the interaction between life events and the development of depression, anxiety, and somatic symptoms remains unclear. ObjectiveTo explore the relationship between life events and the development of depressive, anxiety and somatic symptoms in graduate students, thereby informing prevention strategies for these conditions. MethodsA sample of 6 722 newly enrolled graduate students at a comprehensive university in Southwest China from September to November 2018 was selected. The assessment was conducted using the Adolescent Self-rating Life Events Checklist (ASLEC), the 7-item Generalized Anxiety Disorder scale-7 item (GAD-7), the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Patient Health Questionnaire-15 (PHQ-15). Network analysis was implemented by using the bootnet and qgraph packages in the R software (version 4.2.3), with centrality indices calculated to identify core and bridge symptoms within the network. ResultsThe study encompassed a total of 6 171 graduate students, representing 91.80% of the target population. The prevalence rates of anxiety, depressive, and somatic symptoms among graduate students were 12.59% (777/6 171), 16.63% (1 026/6 171), and 27.66% (1 707/6 171), respectively. Network analysis revealed that 'academic stress' was the core symptom with the highest strength and expected influence (both values=1.207), while 'feeling down, depressed, or hopeless' was the bridge symptom with the highest bridge strength and bridge expected influence (both values=0.454). There was no significant difference in global network strength and edge weight between women and men (P>0.05). ConclusionAcademic stress, emerging as the core symptom, assumes a dominant position within the symptom network and exhibits strong interactions with other negative affective states. There was no gender difference in the network structure.
5.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine(Part 4): Evidence Retrieval and Evaluation
Fuqiang ZHANG ; Lijiao YAN ; Ziteng HU ; Yujing ZHANG ; Yaxin CHEN ; Xingyu ZONG ; Zhao CHEN ; Weili WANG ; He LI ; Ning LIANG ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(1):60-65
The retrieval and evaluation of evidence is the basis for the development of clinical practice guidelines for Chinese patent medicine. As traditional Chinese medicine has a different development trajectory and utilization characteristics from modern medicine, there is certain differences in terms of evidence composition, retrieval and integration.This paper discussed multi-source body of evidence on Chinese patent medicine based on modern evidence-based medicine and ancient medical literature, and summarized the retrieval strategy as well as the possible problems and solving methods. For different types of evidence on Chinese patent medicine, the corresponding evaluation tools have been recommended, and the order to integrate the evidence based on the quality of the evidence from high to low is suggested. Finally, a multi-source based evidence retrieval-evaluation-integration scheme for Chinese patent medicine has been formed, which will provide a methodological reference for practitioners in the development of clinical practice guidelines for Chinese patent medicine.
6.Effect of external mechanical forces on the crystallographic solid form and dissolution rate of traditional Chinese medicine extracts——taking Ligustrum lucidum extract as an example
Linlin LIANG ; Zhiwei WANG ; Xiaoshuang HE ; Weili HENG ; Shuai QIAN ; Yuan GAO ; Jianjun ZHANG ; Yuanfeng WEI
Journal of China Pharmaceutical University 2024;55(6):767-774
Taking the Ligustrum lucidum extract as an example, this study investigated the influence of external mechanical forces under different processing conditions on the crystallographic solid form and the key parameter of drug dissolution rate, so as to provide guidance for the preparation and quality control of traditional Chinese medicine preparations. Under different pulverization and tableting conditions, the change of crystallographic solid form of L. lucidum extract was observed by polarizing light microscope. Meanwhile, the effect of this change on the dissolution rate was investigated, and the mathematical relationship between crystal content and dissolution rate was analyzed. The results showed that the process of ball milling and tableting had a significant impact on the crystallographic solid form of L. lucidum extract. The amorphous extract displayed crystal transformation, which induced a significant decline in dissolution rate. Further studies revealed that there was a negative linear relationship between crystal content and dissolution rate. The results of this study indicated that the crystallographic solid form transformation of traditional Chinese medicine extracts might occur during the preparation process, which may cause potential risks to the quality of traditional Chinese medicine preparations. It is suggested that we should pay attention to and strengthen the investigation of the crystallographic solid form during the preparation process, so as to guarantee the safety, effectiveness, and quality controllability of traditional Chinese medicine preparations.
7.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
8.Analysis of clinicopathological features, therapeutic efficacy, prognosis and mutation in 11 patients with cardiac diffuse large B-cell lymphoma
Na ZHAO ; Qing SHI ; Shu CHENG ; Li WANG ; Pengpeng XU ; Weili ZHAO
Journal of Leukemia & Lymphoma 2024;33(2):97-103
Objective:To investigate the clinicopathological features, mutation, therapeutic efficacy and the factors influencing the prognosis of patients with cardiac diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 cardiac DLBCL patients in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to October 2020 were retrospectively analyzed. NovaSeq sequencing platform was used to detect gene mutations in 5 patients, and bioinformatics analysis of sequencing data was conducted through public database to identify the mutation sites of pathogenic genes. Kaplan-Meier method was used to analyze the progression-free survival (PFS) and the overall survival (OS). Univariate Cox proportional risk model was used to analyze the influencing factors of prognosis.Results:Among 11 patients with cardiac DLBCL, 5 were male and 6 were female. The age [ M ( Q1, Q3)] was 61 years (45 years, 70 years). All 11 patients were non-germinal center B-cell (non-GCB) type. There were 2 primary cases and 9 secondary cases; 9 cases with Ann Arbor stage of Ⅲ-Ⅳ, 10 cases with increased lactate dehydrogenase (LDH) and 9 cases with international prognostic index (IPI) score equal to or higher than 3 scores. Among 11 patients, 9 cases received a first-line treatment based on the R-CHOP (rituximab, cyclophosphamide, epirubicin/doxorubicin hydrochloride liposomes, vincristine and prednisone) regimen, of which 8 patients achieved complete remission (CR), and 1 patient achieved stable disease (SD); 1 patient received IR2 (ibrutinib + rituximab + lenalidomide) treatment regimen and achieved SD, and 1 patient received supportive treatment only and achieved progression of the disease. The follow-up time was 39.9 months (25.6 months, 57.3 months). The 3-year PFS rate and 3-year OS rate of 11 patients was 54.5%, 77.9 %, respectively. Univariate Cox regression analysis showed that gender, B symptoms, Ann Arbor stage, LDH level, number of extranodal lesions, IPI score were not correlated with PFS and OS of patients (all P > 0.05). Among 5 cases undergoing gene detection, KMT2D mutations and PIM1 mutations were detected in 2 cases,respectively. Interestingly, KMT2D mutations were only found in secondary cardiac DLBCL patients (2/3), while PIM1 mutations were only detected in primary cardiac DLBCL patients (2/2). Conclusions:Most cardiac DLBCL patients are non-GCB type and have advanced clinical stage, while may benefit from R-CHOP treatment regimen. PIM1 and KMT2D are the commonly mutated genes in cardiac DLBCL.
9.Clinicopathologic characteristics,gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma
Zhishan DU ; Yue WANG ; Ziyang SHI ; Qing SHI ; Hongmei YI ; Lei DONG ; Li WANG ; Shu CHENG ; Pengpeng XU ; Weili ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(1):64-71
Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.
10.Gut microbiota aids in differentiating proximal colorectal cancer in the combination of tumor markers
Tianchen HUANG ; Xiaodong HAN ; Yong ZHANG ; Kan LI ; Zhipeng GUO ; Lei LI ; Yachao WU ; Yanjun WANG ; Dongxiao BAI ; Jianan XIAO ; Jiangman ZHAO ; Fuyou ZHOU ; Weili LI
Chinese Journal of Laboratory Medicine 2024;47(4):444-450
Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

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